ICAM‐3 (CD50) cross‐linking augments signaling in CD3‐activated peripheral human T lymphocytes

ICAM‐3 is a pan‐hematopoietic, constitutive adhesion molecule. ICAM‐3 binds to LFA‐1 on antigen‐presenting cells (APC) stabilizing the T cell‐APC interaction, facilitating signaling through the CD3/TCR complex. However, recent evidence using cultured and transformed T cells suggests ICAM‐3 may also function in signaling. Because ICAM‐3 is constitutively expressed on resting T cells, we postulated that signaling through ICAM‐3 in resting T cells represents an important costimulatory mechanism in these cells. In purified resting human T cells, cross‐linking both ICAM‐3 and CD3 with plate‐bound antibodies resulted in a marked increase in cell size (consistent with blastogenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM‐3 and CD3 stimulation significantly ( P < 0.001) increased resting human T cell phosphatidylinositol hydrolysis and phospholipase C‐γ1 phosphorylation. These results indicate that ICAM‐3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step. J. Leukoc. Biol. 65: 867–874; 1999.